Des-γ-carboxy prothrombin is a potential autologous growth factor for hepatocellular carcinoma

Mayumi Suzuki, Hidenori Shiraha, Tatsuya Fujikawa, Nobuyuki Takaoka, Naoki Ueda, Yutaka Nakanishi, Kazuko Koike, Akinobu Takaki, Yasushi Shiratori

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94 Citations (Scopus)

Abstract

Des-γ-carboxyl prothrombin (DCP) is a well recognized tumor marker for hepatocellular carcinoma (HCC). In the present study, we demonstrate that DCP has a mitogenic effect on HCC cell lines. Purified DCP stimulated DNA synthesis of Hep3B and SK-Hep-1 cells in a dose-dependent manner. DCP was found to bind with cell surface receptor Met causing Met autophosphorylation and also to activate STAT3 signaling pathway through Janus kinase 1. Luciferase gene reporter analysis showed that DCP induced STAT3-related transcription. Small interfering RNAs against both STAT3 and Met abrogated DCP-induced cell proliferation. DCP did not affect the mitogen-activated protein kinase pathway, Myc signaling pathway, or phosphoinositide 3-kinase/Akt pathway. Based on these results, we believe that DCP acts as an autologous mitogen for HCC cell lines. The Met-Janus kinase 1-STAT3 signaling pathway may be a major signaling pathway for DCP-induced cell proliferation.

Original languageEnglish
Pages (from-to)6409-6415
Number of pages7
JournalJournal of Biological Chemistry
Volume280
Issue number8
DOIs
Publication statusPublished - Feb 25 2005

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ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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